This invention relates to the parenteral administration of solid drug compositions.
Drugs are administered parenterally, e.g., by injection of drug solutions, for various reasons. For example, injection, rather than oral administration, is used for compounds which partially or totally degrade in the gastrointestinal tract. Injections are also preferred when a rapid response is required, i.e., where the time lag between oral administration of the drug and its action on the target site is too long. In addition, the effective use of drugs often requires continuous, controlled parenteral administration to achieve the desired effect. This type of prolonged parenteral administration also has been achieved by the injection of drug solutions.
The continuous parenteral delivery of drugs can be accomplished by mechanical perfusion devices that include a catheter and needle, or by sustained release compositions that typically include a drug and a carrier such as polylactide polymers that retards the release of the drug so that it is slowly dispensed over time. See, e.g., Boswell et al., U.S. Pat. No. 3,773,919, and Hutchinson, U.S. Pat. No. 5,004,602.
Perfusion devices include wearable devices that are powered by electrical or mechanical force. Such devices are generally quite large, often being between 40 cm.sup.3 and 1000 cm.sup.3 in volume. As a result, these devices may cause physical inconvenience to the patient. Electrically powered devices can be designed to be reused upon changing the catheter and needle after each use, whereas mechanically powered devices are generally designed to be disposable.
Electrically powered pumps include syringe pumps, in which a mechanical screw depresses a plunger on a syringe, and peristaltic pumps, in which a rotating wheel exerts pressure on a tube to inject a liquid drug solution into a patient. Piezoelectric pumps have also been used to inject small quantities of liquid drug solutions into patients. Mechanically powered wearable pumps are powered by osmotic pressure, gas or air pressure, or mechanical spring forces.
Although the injection of liquid drug solutions offers certain advantages, the liquid solutions used for injection are associated with a number of disadvantages that arise from the use of necessarily large volumes of liquid excipients. For a normal injection, e.g., by syringe and needle, the drug to be administered must be soluble or capable of suspension in water or other therapeutically acceptable liquid excipient. However, a significant volume of liquid is often needed for the suspension or dissolution of even a small amount of an active drug compound. For example, weight ratios of drug to excipient of 1:100 or even 1:1000 are used. This large volume can make injections uncomfortable or even painful to a patient, especially for patients who are required to have an injection at least once a day for months or even a lifetime, e.g., diabetics who require one or two daily injections of insulin. In addition, drugs are often less stable when mixed into excipient solutions, and the extemporaneous reconstitution of a sterile solution is always associated with an inherent risk of contamination.